Migraine + Anti-emetic Flashcards by Serinna Singh

What are the four components of migraine syndrome?

PRODROME
= vague changes in mood, appetite

AURA
= neurological disturbances

HEADACHE

RESOLUTION

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Characterize a migraine headache

Throbbing

Usually one-sided

N/V, gastric stasis, photophobia, and/or phonophobia

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What is the neurovascular theory?

Abnormal neural activation

Leads to…
Vasodilation, local inflammation
= MIGRAINE!

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What is cortical spreading depression (CSD)?

Wave of strong depolarization that spreads slowly over the cortical surface

Followed by prolonged depression

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What happens following CSD cording to neurovascular theory for migraine?

CSD in cortex leads to release of K+, H+, NO and PGs into interstitial fluid.

These mediators cross meningeal blood vessel and stimulate nerve endings

Substance P and CGRP are released and can lead to release of inflammatory mediators from mast cells, and plasma extravasation

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What class of drugs are very effective against migraine,

Decreasing release of
Substance P
CGRP
Vasoconstriction

5-HT agonists

1B and 1D

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What are general therapies for acute migraine?

NSAIDs (+/- caffeine)

Antiemetics
+Metoclopramide

Opioid analgesics = last resort!

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What are specific therapies for acute migraine?

5-HT (1B/1D) agonists
= “triptans”
= sumatriptan

Ergo Alkaloids
= Ergotamine, Dihydroergotamine

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What are adverse effects of “triptans”?

Paresthesias, flushing, fatigue, dizziness, nausea

Heavy/tightness in chest

Peripheral vasoconstriction + vasospasm

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What are CIs for “triptans”?

CAD

Cerebrovascular disease

PVD

Uncontrolled HTN

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What are DDIs associated with “triptans”?

Metabolized by MAO
- MAO inhibitors

Used in caution with patients taking SSRIs or SNRIs to avoid serotonin syndrome

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What AEs are associated with ergot alkaloids?

N/V

Can cause fetal distress and uterine contractions

Fibrotic thickening of cardiac valves

Peripheral vasoconstriction ‼️‼️

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What are symptoms of ergot poisoning?

Vascular occlusion

limb ischemia

Gangrene

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What are CIs associated with ergot alkaloids?

CAD

PVD

Uncontrolled HTN

Pregnancy

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What are prophylactic agents for migraine?

1st line =
+beta antagonists (propranolol, timolol, metoprolol)
+antiepileptic drugs (valproic acid, divalproex, topiramate)
+antidepressants (amitriptyline, venlafaxine)

ACEIs, ARBs (lisinopril, candesartan)
CCBs (verapamil)
Muscle relaxants (Botox)

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What are alternative therapies for prevention of migraine?

Butterbur extract
**best evidence

CoQ10
Feverfew
Riboflavin
Mg
Melatonin

What receptors when stimulated involve N/V?

5HT3
D2

mAChR
H1

NK1

What inputs contribute to the vomiting response?

Chemoreceptor trigger zone (CTZ) = 5HT3, D2, opioid, NK1(?)

Vestibular apparatus =mAChR, H1

Higher centers = odor, tastes, fear

Stomach Small intestine = 5HT3

Pharynx = gagging

What are causes of 5HT3 mediated emetic effects?

CINV

Radiation

Acute gastroenteritis

Aspirin, ferrous sulfate, other drugs

Surgery

(Serotonin released by intestinal irritants)

What are examples of 5HT3 antagonists?

“Setrons”

What are AEs associated with 5HT3 antagonists?

Mild headache/dizziness
Constipation

All (except palonosetron) can inc. QT interval

What are indications for 5HT3 antagonists?

Acute CINV
(Enhanced with NK1 antagonist and corticosteroid)

RINV

PONV

Acute gastroenteritis induced NV

What are examples of DA agonists?

How do they contribute to emetic effects?

Can induce NV by stimulating D2 receptors in CTZ

Ropinirole
Pramipexole
Rotigotine

What are examples of D2 ANTAgonists ???

Proclorperazine

Chlorpromazine

Metoclopramide

What can D2 antagonists for antiemetic effects lead to?

Can cause EPS (Motor symptoms from dopamine blockade) Diphenhydramine can be administered to prevent or attenuate acute dystonia when agents given parenterally at high doses

What is the black box warning associated with a D2 antagonist antiemetic agent?

Metoclopramide Chronic use => tardive dyskinesia

What are indications for phenothiazines and metoclopramide?

Phenothiazines =general purpose (not CINV) ``` Metoclopramide +PONV +migraine-induced NV +GI motility disorders +CINV ```

What mAChR antagonist is used for antiemetic effects?

Scopolamine

What AEs and CIs are associated with scopolamine?

AEs - Xerostomia - constipation - urinary retention - drowsiness - visual disturbances CIs/cautions: - glaucoma - GI, urinary tract obstruction - BPH

What H1 antihistamines are used as antiemetic agents?

Diphenhydramine Dimenhydrinate Meclizine

What are examples of NK1 receptor antagonists used as antiemetic agents?

"Pitants" Aprepitant Netupitant Rolapitant

What are indications for NK1 receptor antagonists?

CINV PONV = aprepitant

What corticosteroid is used as an antiemetic? What are the indications?

Dexamethasone CINV PONV

What cannabinoids are used for antiemetic function? What are the indications and AEs?

Dronabinol Nabilone indication: CINV AEs: - euphoria/dysphoria - vertigo - paranoia - inc. appetite

When are benzodiazepines used as antiemetics?

Weak antiemetic effects used as adjunct to prevent CINV and PONV